In healthy individuals, the kidney functions to remove excess water, salts and small proteins from the blood circulation. Nitrogenous wastes removed by the kidney include urea, the final metabolic destiny of excess dietary nitrogen, creatinine which is produced during muscle activity, and uric acid, an endpoint product of nucleotide metabolism. Current renal dialysis technology relies on equilibrium/diffusion principles and transmembrane pressure to remove nitrogenous wastes, salts and excess water from the bloodstream of patients experiencing chronic or acute renal failure. This requires two to three hours of dialysis treatment on three or four occasions each week. There are significant deficiencies in existing dialysis technologies, including suboptimal biocompatibility of the dialysis membranes used, the inadequacy of existing technology in the removal of some solutes, such as phosphates, and poor removal of low molecular weight proteins such as beta-2 microglobulin. GradiFlow™ technology, or a modification thereof, can be used to perform blood dialysis for purposes of renal replacement therapy, such that these deficiencies in conventional dialysis could be addressed. These deficiencies can be addressed by including the application of an electrical potential through a blood dialysis chamber to accelerate the removal of charged solutes such as phosphate ions and proteins, as well as charged nitrogenous wastes and other salt ions such as sodium, potassium, chloride and so on. The demonstrated protein separation capacity of the GradiFlow™ technology can be applied to the removal of specific proteins from the blood or plasma circulations, with the intention of treating disease symptoms mediated by those proteins. Examples of such disease states include rheumatoid arthritis and a host of other autoantibody mediated autoimmune diseases, which could be treated by the selective removal of autoantibody or other disease related proteins from the patients blood circulation.
The present inventors have developed a device based on GradiFlow™ technology (AU 601040) which can be used to selectively remove solutes, metabolites and proteins from either blood or plasma. Such a device can be used as either an add-on module to existing dialysis machines, or as a stand-alone device used to filter the blood of dialysis patients as a specific therapeutic measure to remove metabolites and proteins after conventional dialysis therapy has already been applied.
One of the key advantages of the GradiFlow™ is its capacity to desalt. In the present system, this is achieved by the retention of the desired macromolecule in a chamber sandwiched between two restriction membranes. Essentially the GradiFlow™ can be re-configured so that dialysis of a mixture of components is possible.
Internationally, 800,000 people suffer from chronic renal failure which implies that their kidneys can never perform the way they should. In medicine, dialysis is a therapy which eliminates the toxic wastes from the body due to kidney failure. There are two types of dialysis a) haemodialysis and b) peritoneal dialysis.
Haemodialysis is usually performed in dialysis centers, where the treatment entails dialysis for 4 hours three times a week. This sharply interferes with the quality of life of patients and also their productivity to the community at large. The present technology entails the re-routing of blood from the body to a filter made of plastic capillaries. The blood is purified when the waste products diffuse from the blood across the membrane of these tiny capillaries. The blood is then return to the body via the arm. The main advantage to this system is that patient training is not required. The main disadvantages are that dialysis graft failure is common and there is lack of freedom on the part of the patient because of the requirement to report to a center for treatment.
In peritoneal dialysis, the body's own membrane is used as a filter, and the fluid drained in and out of the abdomen replaces the kidneys in getting rid of toxins. There are some great advantages to this system which include the fact that this can be done at home. The domestic use of this, however, requires careful technique and has the added disadvantage of peritonitis and membrane failure.
Gradiflow™ Technology
The Gradiflow™ is a unique preparative electrophoresis technology for macromolecule separation which utilizes tangential flow across a polyacrylamide membrane, such as a selective membrane composed of polyacrylamide hydrogel, when a charge is applied across the membrane. The general design of the Gradiflow™ system facilitates the purification of proteins and other macromolecules under near native conditions, that is under conditions in which the pressure across solvent streams is substantially equal. This results in higher yields and excellent recovery.
In essence, the Gradiflow™ technology is bundled into a cartridge comprising of three or more membranes, at least one of which is a selective membrane composed of polyacrylamide hydrogel, housed in a system of specially engineered grids and gaskets which allow separation of macromolecules by charge and/or molecular weight, while the pressure in the solvent streams are substantially equal. The system can also concentrate and desalt/dialyse at the same time. The multimodal nature of the system allows this technology to be used in a number of other areas especially in therapy for the dialysis of blood in situations like renal failure. The configuration of the Gradiflow™ apparatus containing a selective membrane composed of polyacrylamide hydrogel, and in which the pressure in the solvent streams Are substantially equal allows the possibility of producing a simple portable device which will have the dual capacity of being easy to use an concurrently producing high quality dialysis.